Oculomotor Abnormalities during Reading in the Offspring of Late-Onset Alzheimer's Disease.

INTRODUCTION: Eye movement patterns during reading are well defined and documented. Each eye movement ends up in a fixation point, which allows the brain to process the incoming information and program the following saccade. In this work, we investigated whether eye movement alterations during a reading task might be already present in middle-aged, cognitively normal offspring of late-onset Alzheimer's disease (O-LOAD). METHODS: 18 O-LOAD and 18 age-matched healthy individuals with no family history of LOAD participated in the study. Participants were seated in front of a 20-inch LCD monitor, and single sentences were presented on it. Eye movements were recorded with an eye tracker with a sampling rate of 1000 Hz. RESULTS: Analysis of eye movements during reading revealed that O-LOAD displayed more fixations, shorter saccades, and shorter fixation durations than controls. CONCLUSION: The present study shows that O-LOAD experienced alterations in their eye movements during reading. O-LOAD eye movement behavior could be considered an initial sign of oculomotor impairment. Hence, the evaluation of eye movement during reading might be a useful tool for monitoring well-defined cognitive resources.

Visual Processing during Short-Term Memory Binding in Mild Alzheimer's Disease.

Patients with Alzheimer's disease (AD) typically present with attentional and oculomotor abnormalities that can have an impact on visual processing and associated cognitive functions. Over the last few years, we have witnessed a shift toward the analyses of eye movement behaviors as a means to further our understanding of the pathophysiology of common disorders such as AD. However, little work has been done to unveil the link between eye moment abnormalities and poor performance on cognitive tasks known to be markers for AD patients, such as the short-term memory-binding task. We analyzed eye movement fixation behaviors of thirteen healthy older adults (Controls) and thirteen patients with probable mild AD while they performed the visual short-term memory binding task. The short-term memory binding task asks participants to detect changes across two consecutive arrays of two bicolored object whose features (i.e., colors) have to be remembered separately (i.e., Unbound Colors), or combined within integrated objects (i.e., Bound Colors). Patients with mild AD showed the well-known pattern of selective memory binding impairments. This was accompanied by significant impairments in their eye movements only when they processed Bound Colors. Patients with mild AD remarkably decreased their mean gaze duration during the encoding of color-color bindings. These findings open new windows of research into the pathophysiological mechanisms of memory deficits in AD patients and the link between its phenotypic expressions (i.e., oculomotor and cognitive disorders). We discuss these findings considering current trends regarding clinical assessment, neural correlates, and potential avenues for robust biomarkers.

Microsaccadic behavior when developing a complex dynamical activity.

Microsaccade are sensitive to changes of perceptual inputs as well as modulations of cognitive states. There are just a few works analyzing microsaccade while subjects are processing complex information and fewer when doing predictions about upcoming events. To evaluate whether contextual predictability would change microsaccadic behavior, we evaluated microsaccade of twenty one persons when reading 40 regular sentences and 40 proverbs. Analysis of microsaccade during reading proverbs and regular sentences revealed that microsaccade rate on words before maxjump, during maxjump and words after maxjump varied depending on the kind of sentence and on the word predictability. Maxjump was defined as the word with the largest difference between the cloze predictability of two consecutive words. Low and high predictable words demanded less or more microsaccade on words previous, during and on maxjump depending of the semantic context and of the readers' predictions of upcoming words.In summary, the present study shows that microsaccade' rate evidenced significant differences when reading proverbs and regular sentences. Hence, evaluation of microsaccade during reading sentences with different contextual predictability might provide information about specific effect of cue attention on complex task.

Word processing during reading sentences in patients with schizophrenia: evidences from the eyetracking technique.

PURPOSE: The current study analyze the effect of word properties (i.e., word length, word frequency and word predictability) on the eye movement behavior of patients with schizophrenia (SZ) compared to age-matched controls. METHOD: 18 SZ patients and 40 age matched controls participated in the study. Eye movements were recorded during reading regular sentences by using the eyetracking technique. Eye movement analyses were performed using linear mixed models. FINDINGS: Analysis of eye movements revealed that patients with SZ decreased the amount of single fixations, increased their total number of second pass fixations compared with healthy individuals (Controls). In addition, SZ patients showed an increase in gaze duration, compared to Controls. Interestingly, the effects of current word frequency and current word length processing were similar in Controls and SZ patients. The high rate of second pass fixations and its low rate in single fixation might reveal impairments in working memory when integrating neighbor words. In contrast, word frequency and length processing might require less complex mechanisms, which were functioning in SZ patients. CONCLUSION: To the best of our knowledge, this is the first study measuring how patients with SZ process dynamically well-defined words embedded in regular sentences. The findings suggest that evaluation of the resulting changes in eye movement behavior may supplement current symptom-based diagnosis.

Contextual predictability enhances reading performance in patients with schizophrenia.

In the present work we analyzed fixation duration in 40 healthy individuals and 18 patients with chronic, stable SZ during reading of regular sentences and proverbs. While they read, their eye movements were recorded. We used lineal mixed models to analyze fixation durations. The predictability of words N-1, N, and N+1 exerted a strong influence on controls and SZ patients. The influence of the predictabilities of preceding, current, and upcoming words on SZ was clearly reduced for proverbs in comparison to regular sentences. Both controls and SZ readers were able to use highly predictable fixated words for an easier reading. Our results suggest that SZ readers might compensate attentional and working memory deficiencies by using stored information of familiar texts for enhancing their reading performance. The predictabilities of words in proverbs serve as task-appropriate cues that are used by SZ readers. To the best of our knowledge, this is the first study using eyetracking for measuring how patients with SZ process well-defined words embedded in regular sentences and proverbs. Evaluation of the resulting changes in fixation durations might provide a useful tool for understanding how SZ patients could enhance their reading performance.

Patients with Mild Alzheimer's Disease Fail When Using Their Working Memory: Evidence from the Eye Tracking Technique.

Patients with Alzheimer's disease (AD) develop progressive language, visuoperceptual, attentional, and oculomotor changes that can have an impact on their reading comprehension. However, few studies have examined reading behavior in AD, and none have examined the contribution of predictive cueing in reading performance. For this purpose we analyzed the eye movement behavior of 35 healthy readers (Controls) and 35 patients with probable AD during reading of regular and high-predictable sentences. The cloze predictability of words N - 1, and N + 1 exerted an influence on the reader's gaze duration. The predictabilities of preceding words in high-predictable sentences served as task-appropriate cues that were used by Control readers. In contrast, these effects were not present in AD patients. In Controls, changes in predictability significantly affected fixation duration along the sentence; noteworthy, these changes did not affect fixation durations in AD patients. Hence, only in healthy readers did predictability of upcoming words influence fixation durations via memory retrieval. Our results suggest that Controls used stored information of familiar texts for enhancing their reading performance and imply that contextual-word predictability, whose processing is proposed to require memory retrieval, only affected reading behavior in healthy subjects. In AD patients, this loss reveals impairments in brain areas such as those corresponding to working memory and memory retrieval. These findings might be relevant for expanding the options for the early detection and monitoring in the early stages of AD. Furthermore, evaluation of eye movements during reading could provide a new tool for measuring drug impact on patients' behavior.

Patients with mild Alzheimer's disease produced shorter outgoing saccades when reading sentences.

In the present work we analyzed forward saccades of thirty five elderly subjects (Controls) and of thirty five mild Alzheimer's disease (AD) during reading regular and high-predictable sentences. While they read, their eye movements were recorded. The pattern of forward saccade amplitudes as a function of word predictability was clearly longer in Controls. Our results suggest that Controls might use stored information of words for enhancing their reading performance. Further, cloze predictability increased outgoing saccades amplitudes, as this increase stronger in high-predictable sentences. Quite the contrary, patients with mild AD evidenced reduced forward saccades even at early stages of the disease. This reduction might reveal impairments in brain areas such as those corresponding to working memory, memory retrieval, and semantic memory functions that are already present at early stages of AD. Our findings might be relevant for expanding the options for the early detection and monitoring of in the early stages of AD. Furthermore, eye movements during reading could provide a new tool for measuring a drug's impact on patient's behavior.

Diagnosis of mild Alzheimer disease through the analysis of eye movements during reading.

Reading requires the integration of several central cognitive subsystems, ranging from attention and oculomotor control to word identification and language comprehension. Reading saccades and fixations contain information that can be correlated with word properties. When reading a sentence, the brain must decide where to direct the next saccade according to what has been read up to the actual fixation. In this process, the retrieval memory brings information about the current word features and attributes into working memory. According to this information, the prefrontal cortex predicts and triggers the next saccade. The frequency and cloze predictability of the fixated word, the preceding words and the upcoming ones affect when and where the eyes will move next. In this paper we present a diagnostic technique for early stage cognitive impairment detection by analyzing eye movements during reading proverbs. We performed a case-control study involving 20 patients with probable Alzheimer's disease and 40 age-matched, healthy control patients. The measurements were analyzed using linear mixed-effects models, revealing that eye movement behavior while reading can provide valuable information about whether a person is cognitively impaired. To the best of our knowledge, this is the first study using word-based properties, proverbs and linear mixed-effect models for identifying cognitive abnormalities.

Lack of contextual-word predictability during reading in patients with mild Alzheimer disease.

In the present work we analyzed the effect of contextual word predictability on the eye movement behavior of patients with mild Alzheimer disease (AD) compared to age-matched controls, by using the eyetracking technique and lineal mixed models. Twenty AD patients and 40 age-matched controls participated in the study. We first evaluated gaze duration during reading low and highly predictable sentences. AD patients showed an increase in gaze duration, compared to controls, both in sentences of low or high predictability. In controls, highly predictable sentences led to shorter gaze durations; by contrary, AD patients showed similar gaze durations in both types of sentences. Similarly, gaze duration in controls was affected by the cloze predictability of word N and N+1, whereas it was the same in AD patients. In contrast, the effects of word frequency and word length were similar in controls and AD patients. Our results imply that contextual-word predictability, whose processing is proposed to require memory retrieval, facilitated reading behavior in healthy subjects, but this facilitation was lost in early AD patients. This loss might reveal impairments in brain areas such as those corresponding to working memory, memory retrieval, and semantic memory functions that are already present at early stages of AD. In contrast, word frequency and length processing might require less complex mechanisms, which were still retained by AD patients. To the best of our knowledge, this is the first study measuring how patients with early AD process well-defined words embedded in sentences of high and low predictability. Evaluation of the resulting changes in eye movement behavior might provide a useful tool for a more precise early diagnosis of AD.

Registering eye movements during reading in Alzheimer's disease: difficulties in predicting upcoming words.

Reading requires the fine integration of attention, ocular movements, word identification, and language comprehension, among other cognitive parameters. Several of the associated cognitive processes such as working memory and semantic memory are known to be impaired by Alzheimer's disease (AD). This study analyzes eye movement behavior of 18 patients with probable AD and 40 age-matched controls during Spanish sentence reading. Controls focused mainly on word properties and considered syntactic and semantic structures. At the same time, controls' knowledge and prediction about sentence meaning and grammatical structure are quite evident when we consider some aspects of visual exploration, such as word skipping, and forward saccades. By contrast, in the AD group, the predictability effect of the upcoming word was absent, visual exploration was less focused, fixations were much longer, and outgoing saccade amplitudes were smaller than those in controls. The altered visual exploration and the absence of a contextual predictability effect might be related to impairments in working memory and long-term memory retrieval functions. These eye movement measures demonstrate considerable sensitivity with respect to evaluating cognitive processes in Alzheimer's disease. They could provide a user-friendly marker of early disease symptoms and of its posterior progression.

Eye movement alterations during reading in patients with early Alzheimer disease.

PURPOSE: Eye movements follow a reproducible pattern during normal reading. Each eye movement ends up in a fixation point, which allows the brain to process the incoming information and to program the following saccade. Alzheimer disease (AD) produces eye movement abnormalities and disturbances in reading. In this work, we investigated whether eye movement alterations during reading might be already present at very early stages of the disease. METHODS: Twenty female and male adult patients with the diagnosis of probable AD and 20 age-matched individuals with no evidence of cognitive decline participated in the study. Participants were seated in front of a 20-inch LCD monitor and single sentences were presented on it. Eye movements were recorded with an eye tracker, with a sampling rate of 1000 Hz and an eye position resolution of 20 arc seconds. RESULTS: Analysis of eye movements during reading revealed that patients with early AD decreased the amount of words with only one fixation, increased their total number of first- and second-pass fixations, the amount of saccade regressions and the number of words skipped, compared with healthy individuals (controls). They also reduced the size of outgoing saccades, simultaneously increasing fixation duration. CONCLUSIONS: The present study shows that patients with mild AD evidenced marked alterations in eye movement behavior during reading, even at early stages of the disease. Hence, evaluation of eye movement behavior during reading might provide a useful tool for a more precise early diagnosis of AD and for dynamical monitoring of the pathology.

Interval fuzzy modeling applied to Wiener models with uncertainties.

This correspondence addresses the problem of interval fuzzy model identification and its use in the case of the robust Wiener model. The method combines a fuzzy identification methodology with some ideas from linear programming theory. On a finite set of measured data, an optimality criterion which minimizes the maximum estimation error between the data and the proposed fuzzy model output is used. The min-max optimization problem can then be seen as a linear programming problem that is solved to estimate the parameters of the fuzzy model in each fuzzy domain. This results in lower and upper fuzzy models that define the confidence interval of the observed data. The model is called the interval fuzzy model and is used to approximate the static nonlinearity in the case of the Wiener model with uncertainties. The resulting model has the potential to be used in the areas of robust control and fault detection.